Proteins are useful in a variety of diagnostic, pharmacologic, agricultural, nutritional, and research applications. Given the high cost of producing proteins, especially therapeutic proteins, even small increases in the efficiency of production or in the function and stability of a protein can be valuable.
The function and stability, and hence the utility, of a protein can be affected by the post-translational addition of sugar residues to the protein to form a glycoprotein. For example, the addition of terminal sialic acid residues to polysaccharides attached to a glycoprotein generally increases the protein's lifetime in the bloodstream and can, in particular cases, also affect solubility, thermal stability, resistance to protease attack, antigenicity, and specific activity of some glycoproteins. See e. g. Gu and Wang (1998), Biotechnol. and Bioeng. 58 (6): 642-48; Morell et al. (1968), J. Biol. Chem. 243 (1): 155-59.
Recombinant glycoprotein proteins and drugs produced by cell lines, such as Chinese hamster ovary (CHO) cells, generally consist of differentially sialylated isoforms. Poorly sialylated isoforms have shorter circulatory half-life and are thus less efficacious.
It is therefore desirable to increase the sialic acid content of a glycoprotein, especially a glycoprotein to be used for pharmacologic applications. Indeed, one of the major research focuses in the biotechnology field has been how to increase sialylation of recombinant protein drugs.